The impact of enzyme-inducing antiepileptic drugs on antiretroviral drug levels: A case-control study

Purpose: To evaluate the impact of enzyme-inducing antiepileptic drugs (EI-AEDs) on serum antiretroviral (ARV) levels in patients with HIV. Methods: Data from the U.S. Military HIV Natural History Study were screened to identify participants taking ARVs with EI-AEDs and controls taking ARVs with non enzyme-inducing AEDs (NEI-AEDs). The proportion of serum ARV levels below the recommended minimum concentrations (C-min) was compared between these groups. Results: ARV levels were available for 10 individuals exposed to 16 intervals on combined ARVs/EI-AEDs (phenytoin and carbamazepine) and for 25 controls exposed to 30 overlap intervals on combined ARVs/NEI-AEDs. The percentage of overlap intervals with >= 1 ARV levels below Cmin was higher in the EI-AED group than in controls (37.5% vs. 23.3%; p = 0.124). After excluding intervals associated with serum levels of EI-AEDs below the reference range (n = 6), the proportion of intervals with >= 1 ARV level below C-min was significantly greater among EI-AED recipients (60%) compared to controls (23.3%; p = 0.008). Conclusions: ARV levels below C-min were more common in participants receiving EI-AEDs, the difference being statistically significant for intervals associated with EI-AED levels within the reference range. These data suggest that, in agreement with current guidelines, EI-AEDs should be avoided in patients receiving ARV therapy. (c) 2012 Elsevier B.V. All rights reserved.